ArticleMolecular psychiatry2025
A longitudinal study of hippocampal subfield volumes and hippocampal glutamate levels in antipsychotic-naïve first episode psychosis patients.
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.
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Who cites it
6 citing papers in PubMed.
- Unsupervised Clustering of ACC and Hippocampal Metabolites Identifies Subgroups in Antipsychotic-Naïve First-Episode Psychosis.Schizophrenia bulletin · 2026Article
- Distinct brain volume abnormalities in clinical high-risk individuals: pre- and post-antipsychotic treatment.Psychological medicine · 2026Article
- Distinct subcortical neuroanatomic profiles of treatment-resistant schizophrenia: structural magnetic resonance imaging study.BJPsych open · 2026Article
- A Multimodal Observational Case-Control Study Exploring Gut Microbiota-Hippocampus Alterations in Individuals With High Positive Schizotypy From the General Population.Biological psychiatry global open science · 2025Article
- 3D histological mapping of hippocampal subfields: a comparative study in patients with schizophrenia and healthy controls.Frontiers in psychiatry · 2025Article
- Neuroimaging in schizophrenia: From group-average abnormalities to individualised circuit models.Science progressReview
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Funding
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.
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