Evidence map›Paper›PMID 30946828›Full record

ReviewNeuron2019

Altered Connectivity in Depression: GABA and Glutamate Neurotransmitter Deficits and Reversal by Novel Treatments.

Ronald S Duman, Gerard Sanacora, John H Krystal

2 registry-linked trialsOpen access · bronzeAbstract readReview
In one paragraph

Review in Neuron, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 537 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
537citing papers in PubMed, 6 pooled it
70.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

NCT04780152 phase2 / phase3unknown statusnot on this mapstarted 2021, after this paper: background citation

Assessment of Efficacy and Safety of Anodal Transcranial Direct Current Stimulation (TDCS) in Pediatric and Teenage Patients With Major Depressive Disorder During COVID-19 Pandemics

TypeinterventionalSponsorEl Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco SuarezRan2021 to 2022Enrolled172ConditionsMajor Depressive DisorderArmsTranscranial Direct Current Stimulation, Placebo-simulation of transcranial direct current stimulation, Fluoxetine Tablets
NCT06091163 nacompletednot on this mapstarted 2024, after this paper: background citation

A Randomised Controlled Trial Evaluating the Efficacy and Mechanisms of a Ketogenic Diet as an Adjunctive Treatment for People With Treatment-resistant Depression

TypeinterventionalSponsorUniversity of OxfordRan2024 to 2024Enrolled88ConditionsTreatment Resistant Depression, Depression, Mental Illness, Mental DisorderArmsKetogenic Diet, Phytonutrient Diet
3 · Its place in the literature

Who cites it

537 citing papers in PubMed, 6 syntheses or guidelines pooled it, 966 citations in OpenAlex.

  1. Pooled it
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  14. Beyond Histamine Blockade: Clemastine Fumarate as a Promoter of Myelin Regeneration, Inflammatory Regulation, and Neuroimmune Modulation in CNS Disorders.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026
    Review
  15. Article
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  18. Modulation of GABA and glutamate by ketamine in depression: A systematic review and meta-analysis of magnetic resonance spectroscopy studies.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Article
  19. Article
  20. Article

477 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Ronald S DumanDepartment of Psychiatry, Yale University School of Medicine, 34 Park Street, New Haven, CT 06508, USA. Electronic address: ronald.duman@yale.edu.
Gerard SanacoraDepartment of Psychiatry, Yale University School of Medicine, 34 Park Street, New Haven, CT 06508, USA.
John H KrystalDepartment of Psychiatry, Yale University School of Medicine, 34 Park Street, New Haven, CT 06508, USA.
Yale University · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
YALE UNIVERSITY CLINICAL AND TRANSLATIONAL SCIENCE AWARD PROGRAMUL1RR024139 · NCRR · YALE UNIVERSITY · PI SHERWIN, ROBERT S · 2006 to 2011
$56.8M
Translational Technologies CoreP50AA012870 · NIAAA · YALE UNIVERSITY · PI John H. Krystal · 2001 to 2026
$43.7M
Role of mTOR and Synaptogenesis in the Actions of Rapid-Acting AntidepressantsR01MH093897 · NIMH · YALE UNIVERSITY · PI DILEONE, RALPH J · 2011 to 2021
$5.0M
Antidepressants: Signal Transduction and Gene ExpressionR37MH045481 · NIMH · YALE UNIVERSITY · PI DUMAN, RONALD S. · 2005 to 2014
$3.5M
Synaptic mechanisms underlying the rapid antidepressant actions of scopolamineR01MH105910 · NIMH · YALE UNIVERSITY · PI PICCIOTTO, MARINA R · 2014 to 2018
$2.2M
ANTIDEPRESSANTS AND SIGNAL TRANSDUCTION IN BRAINR01MH045481 · NIMH · YALE UNIVERSITY · PI DUMAN, RONALD S. · 1995 to 2004
$1.3M
NCATS NIH HHS UL1 TR001863NCRR NIH HHS UL1 RR024139NIAAA NIH HHS P50 AA012870NIMH NIH HHS R01 MH045481NIMH NIH HHS R01 MH093897NIMH NIH HHS R01 MH105910NIMH NIH HHS R37 MH045481
6 · The paper itself

Abstract

The mechanisms underlying the pathophysiology and treatment of depression and stress-related disorders remain unclear, but studies in depressed patients and rodent models are beginning to yield promising insights. These studies demonstrate that depression and chronic stress exposure cause atrophy of neurons in cortical and limbic brain regions implicated in depression, and brain imaging studies demonstrate altered connectivity and network function in the brains of depressed patients. Studies of the neurobiological basis of the these alterations have focused on both the principle, excitatory glutamate neurons, as well as inhibitory GABA interneurons. They demonstrate structural, functional, and neurochemical deficits in both major neuronal types that could lead to degradation of signal integrity in cortical and hippocampal regions. The molecular mechanisms underlying these changes have not been identified but are thought to be related to stress induced excitotoxic effects in combination with elevated adrenal glucocorticoids and inflammatory cytokines as well as other environmental factors. Transcriptomic studies are beginning to demonstrate important sex differences and, together with genomic studies, are starting to reveal mechanistic domains of overlap and uniqueness with regards to risk and pathophysiological mechanisms with schizophrenia and bipolar disorder. These studies also implicate GABA and glutamate dysfunction as well as immunologic mechanisms. While current antidepressants have significant time lag and efficacy limitations, new rapid-acting agents that target the glutamate and GABA systems address these issues and offer superior therapeutic interventions for this widespread and debilitating disorder.

Indexed as

AnimalsAntidepressive AgentsBrainCerebral CortexDepressive Disordergamma-Aminobutyric AcidGlutamic AcidHippocampusHumansInterneuronsKetamineNeuronsSex FactorsSynaptic TransmissionAntidepressive Agentsgamma-Aminobutyric AcidGlutamic AcidKetamine

Identifiers

PMID30946828
PMCPMC6450409
OpenAlexW2933289315

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.