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ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2026

7T magnetic resonance spectroscopic imaging of subcortical neurometabolites across antipsychotic treatment in acutely symptomatic early-phase schizophrenia spectrum disorders.

Michael Pupi, Andrew E Papale, Finnegan J Calabro, Samira Raminfard, Annie Blazer, Tate Overbey, William Foran, Hoby P Hetherington, Chan H Moon, Beatriz Luna and 1 more

Abstract read
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Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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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

11 authors.

Michael Pupi *Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Andrew E Papale *Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Finnegan J CalabroDepartment of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-8092-3942
Samira RaminfardDepartment of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Annie BlazerDepartment of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Tate OverbeyDepartment of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
William ForanDepartment of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0001-7491-9798
Hoby P HetheringtonResonance Research Incorporated, Billerica, MA, USA.
Chan H MoonDepartment of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Beatriz LunaDepartment of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Deepak K SarpalDepartment of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. sarpaldk@upmc.edu.ORCID http://orcid.org/0000-0001-5842-6782

Funding

Refinement of Brain Mechanisms Underlying the Developmental Stabilization from Adolescent to Adult Neurocognitive ProcessingR01MH067924 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BEATRIZ LUNA · 2004 to 2026
$14.0M
A Multidimensional Dissection of Antipsychotic Treatment Response in Early SchizophreniaR01MH124705 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Deepak K Sarpal · 2021 to 2026
$3.3M
Brain and Behavior Research Foundation (Brain & Behavior Research Foundation) Narsad Young Investigator AwardPittsburgh Foundation (TPF) Rising Star AwardU.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01MH067924U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01MH124705
6 · The paper itself

Abstract

Despite growing evidence from magnetic resonance spectroscopy studies of glutamatergic and GABAergic abnormalities in schizophrenia, in vivo characterization of subcortical neurometabolites at ultra-high field and their longitudinal change across antipsychotic treatment remains limited. Ultra-high-field 7-Tesla (7 T) magnetic resonance spectroscopic imaging (MRSI) enables simultaneous multivoxel quantification of neurometabolites across subcortical regions implicated in schizophrenia, including the thalamus and dorsal caudate. Here, we leveraged 7 T MRSI to characterize subcortical neurometabolite profiles in 91 healthy individuals and 29 individuals with early-phase schizophrenia spectrum disorders (SSD) scanned while presenting with moderate to severe psychosis and following eight weeks of antipsychotic treatment. Primary analyses revealed lateralized alterations in glutamate (Glu) and GABA. In the caudate, Glu and Glx were elevated in the right hemisphere, while GABA was elevated on the right and reduced on the left, a dissociation observed in both the caudate and thalamus. Left thalamic Glx was also elevated, and Glu-GABA coupling was disrupted in the right thalamus. In secondary analyses, thalamic NAAG was markedly reduced in the left hemisphere, with elevation observed in the right thalamus, in addition to left-lateralized thalamic and caudate NAA reduction and elevated caudate GPC.Cho. In exploratory treatment-response analyses, non-remitters showed lower left thalamic and caudate NAA and GABA at baseline, with thalamic Glu declining below healthy control levels at follow-up only in non-remitters. Right thalamic NAAG elevation was restricted to the longer illness group. Collectively, these findings implicate an asymmetric disruption of astroglial-neuronal balance within subcortical regions in early-phase SSD, and across antipsychotic treatment.

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Registered trials

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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 Socratic graph.