Evidence map›Paper›PMID 39580605›Full record

ArticleMolecular psychiatry2025

A longitudinal study of hippocampal subfield volumes and hippocampal glutamate levels in antipsychotic-naïve first episode psychosis patients.

Eric A Nelson, Nina V Kraguljac, Adil Bashir, Stacey S Cofield, Jose O Maximo, William Armstrong, Adrienne C Lahti

Abstract read
In one paragraph

Article in Molecular psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

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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

7 authors.

Eric A NelsonDepartment of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, USA.ORCID 0000-0002-4084-8570
Nina V KraguljacDepartment of Psychiatry and Behavioral Health, The Ohio State University, Columbus, USA.ORCID 0000-0003-2567-4098
Adil BashirDepartment of Biostatistics, University of Alabama at Birmingham, Birmingham, USA.
Stacey S CofieldDepartment of Electrical and Computer Engineering, Auburn University, Auburn, USA.
Jose O MaximoDepartment of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, USA.ORCID 0000-0002-7204-8623
William ArmstrongDepartment of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, USA.
Adrienne C LahtiDepartment of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, USA. alahti@uabmc.edu.ORCID 0000-0002-5565-7662

Funding

National Dissemination of I-Corps@NCATS: Accelerating Translation through CommercializationUL1TR003096 · NCATS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI GUTIERREZ, ORLANDO M, KIMBERLY, ROBERT P. · 2019 to 2023
$43.6M
Trajectories of treatment response as window into the heterogeneity of psychosis: a longitudinal multimodal imaging study in medication-naieve first episode psychosis patientsR01MH113800 · NIMH · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI LAHTI, ADRIENNE C · 2018 to 2022
$3.9M
Contribution of Glutamate Excess and Inflammation to Progressive White Matter Changes in PsychosisR01MH118484 · NIMH · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI KRAGULJAC, NINA VANESSA · 2019 to 2023
$3.3M
Glutamate, brain connectivity and duration of untreated psychosisR01MH102951 · NIMH · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI LAHTI, ADRIENNE C · 2014 to 2018
$2.9M
Structural and Neurometabolic White Matter Integrity in the Deficit SyndromeK23MH106683 · NIMH · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI KRAGULJAC, NINA VANESSA · 2015 to 2019
$883k
NCATS NIH HHS UL1 TR003096NIMH NIH HHS K23 MH106683NIMH NIH HHS R01 MH102951NIMH NIH HHS R01 MH113800NIMH NIH HHS R01 MH118484
6 · The paper itself

Abstract

backgroundPrevious studies have implicated hippocampal abnormalities in the neuropathology of psychosis spectrum disorders. Reduced hippocampal volume has been reported across all illness stages, and this atrophy has been hypothesized to be the result of glutamatergic excess. To test this hypothesis, we measured hippocampal subfield volumes and hippocampal glutamate levels in antipsychotic naïve first episode psychosis patients (FEP) and the progression of volume decline and changes in glutamate levels over a 16-week antipsychotic drug (APD) trial. We aimed to determine if subfield volumes at baseline were associated with glutamate levels, and if baseline glutamate levels were predictive of change in subfield volumes over time.

methodsWe enrolled ninety-three medication-naïve FEP participants and 80 matched healthy controls (HC). T1 and T2 weighted images and magnetic resonance spectroscopy (MRS) data from a voxel prescribed in the left hippocampus were collected from participants at baseline and after 6 and 16 weeks of APD treatment. Hippocampal subfield volumes were assessed using FreeSurfer 7.1.1., while glutamate levels were quantified using jMRUI version 6.0. Data were analyzed using linear mixed models.

resultsWe found regional subfield volume deficits in the CA1, and presubiculum in FEP at baseline, that further expanded to include the molecular and granule cell layer of the dentate gyrus (GC/ML/DG) and CA4 by week 16. Baseline hippocampal glutamate levels in FEP were not significantly different than those of HC, and there was no effect of treatment on glutamate. Glutamate levels were not related to initial subfield volumes or volume changes over 16 weeks.

conclusionWe report a progressive loss of hippocampal subfield volumes over a period of 16 weeks after initiation of treatment, suggestive of early progression in neuropathology. Our results do not suggest a role for glutamate as a driving factor. This study underscores the need to further research the mechanism(s) underlying this phenomenon as it has implications for early intervention to preserve cognitive decline in FEP participants.

Indexed as

Glutamic AcidHippocampusPsychotic DisordersAdolescentAdultAntipsychotic AgentsAtrophyFemaleHumansLongitudinal StudiesMagnetic Resonance ImagingMagnetic Resonance SpectroscopyMaleOrgan SizeYoung AdultAntipsychotic AgentsGlutamic Acid

Identifiers

PMID39580605
PMCPMC12014507

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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.