Evidence map›Paper›PMID 41904268›Full record

SynthesisMolecular psychiatry2026

Brain structural abnormalities in treatment-resistant schizophrenia.

Semra Etyemez, Rohit Sivananthan, Andreia V Faria, Felice Iasevoli, Giuseppe Pontillo, Annabella Di Giorgio, Young-Chul Chung, Woo-Sung Kim, Soyolsaikhan Odkhuu, Jun Soo Kwon and 16 more

Abstract readMeta-Analysis
PubMed Publisher
In one paragraph

Synthesis in Molecular psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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

1 citing paper in PubMed.

  1. Article
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

26 authors.

Semra EtyemezDepartment of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Rohit SivananthanDepartment of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Andreia V FariaDepartments of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-1673-002X
Felice IasevoliSection of Psychiatry, Department of Neuroscience, University "Federico II", Naples, Italy.ORCID http://orcid.org/0000-0002-7051-5013
Giuseppe PontilloDepartment of Advanced Biomedical Sciences, University "Federico II", Naples, Italy.
Annabella Di GiorgioASST Papa Giovanni XXIII, Department of Mental Health and Addictions, Bergamo, Italy.
Young-Chul ChungDepartment of Psychiatry, Jeonbuk National University, Medical School, Jeonju, Korea.ORCID http://orcid.org/0000-0001-9491-1822
Woo-Sung KimDepartment of Psychiatry, Jeonbuk National University, Medical School, Jeonju, Korea.
Soyolsaikhan OdkhuuDepartment of Psychiatry, Jeonbuk National University, Medical School, Jeonju, Korea.
Jun Soo KwonDepartment of Psychiatry, Hanyang University Hospital, Seoul, South Korea.ORCID http://orcid.org/0000-0002-1060-1462
Minah KimDepartment of Psychiatry, Seoul National University College of Medicine, Seoul, South Korea.ORCID http://orcid.org/0000-0001-8668-0817
Minji HaDepartment of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, South Korea.
Foivos GeorgiadisDepartment of Adult Psychiatry and Psychotherapy Psychiatric University Clinic Zurich and University of Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0001-8784-9653
Beatrice A MilanoDivision of Adult Psychiatry, Department of Psychiatry, Geneva University Hospitals, Geneva, Switzerland.ORCID http://orcid.org/0000-0001-5064-6385
Matthias KirschnerDivision of Adult Psychiatry, Department of Psychiatry, Geneva University Hospitals, Geneva, Switzerland.ORCID http://orcid.org/0000-0002-9486-1439
Stefan KaiserDivision of Adult Psychiatry, Department of Psychiatry, Geneva University Hospitals, Geneva, Switzerland.
Diana Tordesillas-GutiérrezInstituto de Física de Cantabria UC-CSIC, Santander, Spain.ORCID http://orcid.org/0000-0003-1458-3932
Kang SimWest Region, Institute of Mental Health, Singapore, Singapore.ORCID http://orcid.org/0000-0003-3209-9626
Yunlong TanPeking University HuiLongGuan Clinical Medical School, Beijing HuiLongGuan Hospital, Beijing, China.ORCID http://orcid.org/0000-0002-3522-3912
Sherry Kit Wa ChanDepartment of Psychiatry, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Jessica A TurnerDepartment of Psychiatry and Behavioral Health, Wexner Medical Center, Ohio State University, Columbus, OH, USA.ORCID http://orcid.org/0000-0003-0076-8434
Theo G M van ErpClinical Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA, USA.
Jimmy LeeLee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.ORCID http://orcid.org/0000-0002-7724-7445
Vince D CalhounTri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State, Georgia Tech, Emory, Atlanta, GA, USA.ORCID http://orcid.org/0000-0001-9058-0747
Akira SawaDepartment of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA. asawa1@jhmi.edu.ORCID http://orcid.org/0000-0003-1401-3008
Kun YangDepartment of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA. kunyang@jhmi.edu.ORCID http://orcid.org/0000-0002-1060-8082

Funding

Brain and Behavior Research Foundation (Brain & Behavior Research Foundation) NARSAD young investigator awardCapital Health Research and Development of Special 2022-1-2131Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III) 00/3095Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III) 01/3129Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III) PI020499Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III) PI14/00639Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III) PI14/00918Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III) PI17/01056Ministry of Health and Welfare (Ministry of Health, Welfare and Family Affairs) HL19C0015Ministry of Health and Welfare (Ministry of Health, Welfare and Family Affairs) HR18C0016National Natural Science Foundation of China (National Science Foundation of China) 82171507U.S. Department of Health & Human Services | National Institutes of Health (NIH) MH-094268U.S. Department of Health & Human Services | National Institutes of Health (NIH) MH-107730U.S. Department of Health & Human Services | National Institutes of Health (NIH) MH-121246U.S. Department of Health & Human Services | National Institutes of Health (NIH) MH-123610U.S. Department of Health & Human Services | National Institutes of Health (NIH) MH-129480U.S. Department of Health & Human Services | National Institutes of Health (NIH) MH-1345261U.S. Department of Health & Human Services | National Institutes of Health (NIH) MH-136297
6 · The paper itself

Abstract

Treatment-resistant schizophrenia (TRS) poses a considerable challenge in psychiatric care, with approximately 10-60% of patients exhibiting non-responsiveness to antipsychotic medication. While early treatment could improve clinical outcomes, the absence of objective biomarkers hinders timely intervention. General structural changes have been suggestively associated with TRS. However, there is a lack of clear and robust conclusions due to challenges in obtaining data from TRS cases with large sample sizes. To address this knowledge gap, we collaborated with Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) consortium to investigate brain structural changes associated with TRS. Leveraging data from multiple institutions spanning various continents and ethnic groups, our meta- and mega-analysis revealed a significant reduction in the volume of bilateral putamen and bilateral hippocampus, as well as the left superior frontal gyrus (SFG) surface area in TRS patients compared with non-TRS patients with sufficient statistical power. Further analysis, incorporating data from healthy controls (HCs), unveiled a decreasing trend in bilateral hippocampal volumes and left SFG surface area from HCs to non-TRS patients and further to TRS patients. There were no significant effects of either clozapine dose or cumulative antipsychotic exposure on bilateral hippocampal volumes or left SFG surface area. In contrast, the putamen volume exhibited an increase in non-TRS patients compared with HCs, with no significant difference between TRS patients and HCs. Antipsychotic exposure was significantly correlated with the putamen volume with small effect size. In conclusion, this study underscores the volume of the hippocampus and SFG as potential biomarkers for TRS.

Indexed as

BrainSchizophreniaSchizophrenia, Treatment-ResistantAdultAntipsychotic AgentsClozapineFemaleHippocampusHumansMagnetic Resonance ImagingMaleMiddle AgedPutamenAntipsychotic AgentsClozapine

Identifiers

PMID41904268

What OpenQuestion holds

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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 OpenQuestion graph.