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Record W3155982295 · doi:10.1101/2021.04.09.21255211

Prefrontal glutamate neurotransmission in PTSD: A novel approach to estimate synaptic strength in vivo in humans

2021· preprint· en· W3155982295 on OpenAlexfundno aff
Lynnette A. Averill, Lihong Jiang, Prerana Purohit, Anastasia Coppoli, Christopher L. Averill, Jeremy Roscoe, Benjamin Kelmendi, Henk M. De Feyter, Robin A. de Graaf, Ralitza Gueorguieva, Gerard Sanacora, John H. Krystal, Douglas L. Rothman, Graeme F. Mason, Chadi G. Abdallah

Bibliographic record

VenuemedRxiv · 2021
Typepreprint
Languageen
FieldNeuroscience
TopicNeuroscience and Neuropharmacology Research
Canadian institutionsnot available
FundersNational Institute of Mental HealthNational Institute on Alcohol Abuse and AlcoholismNational Institutes of HealthServierVistagen TherapeuticsGeorgia Clinical and Translational Science AllianceGenentechValeant Pharmaceuticals InternationalYale Center for Clinical Investigation, Yale School of MedicineBristol-Myers SquibbEli Lilly and CompanyAstraZenecaNational Alliance for Research on Schizophrenia and DepressionAmerican Foundation for Suicide PreventionBiogenNational Center for PTSD, U.S. Department of Veterans AffairsGilead SciencesYale UniversitySanofiTeva Pharmaceutical IndustriesH. Lundbeck A/SU.S. Department of Veterans Affairs
KeywordsGlutamatergicNeurotransmissionGlutamate receptorNeurosciencePrefrontal cortexPsychologyMedicineInternal medicineReceptorCognition

Abstract

fetched live from OpenAlex

ABSTRACT Trauma and chronic stress are believed to induce and exacerbate psychopathology by disrupting glutamate synaptic strength. However, in vivo in human methods to estimate synaptic strength are limited. In this study, we established a novel putative biomarker of glutamatergic synaptic strength, termed energy-per-cycle (EPC). Then, we used EPC to investigate the role of prefrontal neurotransmission in trauma psychopathology. Healthy control (n=18) and patients with posttraumatic stress (PTSD; n=16) completed 13 C-acetate magnetic resonance spectroscopy scans to estimate prefrontal EPC, which is the ratio of neuronal energetic needs per glutamate neurotransmission cycle (V TCA /V Cycle ). Patients with PTSD were found to have 28% reduction in prefrontal EPC ( t =3.0; df =32, p =0.005). There was no effect of sex on EPC, but age was negatively associated with prefrontal EPC across groups ( r =–0.46, n=34, p =0.006). Controlling for age did not affect the study results. The feasibility and utility of EPC were established. Patients with PTSD were found to have reduced prefrontal glutamatergic synaptic strength. These findings suggest that reduced glutamatergic synaptic strength may contribute to the pathophysiology of PTSD and could be targeted by new treatments. Highlights Glutamatergic synaptic strength is critical for brain function in health and disease. In vivo in human methods to estimate glutamatergic synaptic strength are limited. We here propose a new approach to estimate glutamatergic synaptic strength. The new method employs carbon-13 magnetic resonance spectroscopy ( 13 C MRS). The utility of the new approach was demonstrated in posttraumatic stress disorder (PTSD).

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.076
GPT teacher head0.365
Teacher spread0.290 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations6
Published2021
Admission routes1
Has abstractyes

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