Evidence map›Paper›PMID 41567988›Full record

ArticleBiological psychiatry global open science2026

Increased Tumor Necrosis Factor Superfamily Members in Neuroinflammatory Schizophrenia and Bipolar Disorder Midbrains.

Gerardo Mendez-Victoriano, Yunting Zhu, Layla Neuhaus, Suhaana Shaik, Frank Middleton, Yuji Kondo, Amir Fayyazuddin, Daniel Hoeppner, Sofía Puvogel, Astrid Alsema and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biological psychiatry global open science, 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

17 authors.

Gerardo Mendez-VictorianoDepartment of Neuroscience and Physiology, Upstate Medical University, Syracuse, New York.
Yunting ZhuDepartment of Neuroscience and Physiology, Upstate Medical University, Syracuse, New York.
Layla NeuhausNeuroscience Research Australia, Sydney, New South Wales, Australia.
Suhaana ShaikNeuroscience Research Australia, Sydney, New South Wales, Australia.
Frank MiddletonDepartment of Neuroscience and Physiology, Upstate Medical University, Syracuse, New York.
Yuji KondoAstellas Pharma Inc., Tokyo, Japan.
Amir FayyazuddinAstellas West Coast Innovation and Research Center, South San Francisco, California.
Daniel HoeppnerAstellas Engineered Small Molecules US, Inc., Cambridge, Massachusetts.
Sofía PuvogelCognitive Neuroscience Section, Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Astrid AlsemaDepartment of Biomedical Sciences, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Laura KrachtDepartment of Biomedical Sciences, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Mitsuyuki MatsumotoArialys Therapeutics, Inc., La Jolla, California.
Bart J L EggenDepartment of Biomedical Sciences, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Adam K WalkerNeuroscience Research Australia, Sydney, New South Wales, Australia.
Maree J WebsterLaboratory of Brain Research, Stanley Medical Research Institute, Rockville, Maryland.
Iris E C SommerCognitive Neuroscience Section, Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Cynthia S WeickertDepartment of Neuroscience and Physiology, Upstate Medical University, Syracuse, New York.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Neuroinflammation is a key neuropathological finding in schizophrenia and bipolar disorder, as increased cytokines are found in the midbrain of these individuals. However, the most upregulated inflammatory cytokines and most activated downstream signaling pathway(s) are unidentified. Methods: We aimed to identify the most robust transcriptional change in the schizophrenia midbrain by bulk RNA sequencing (RNA-seq) and to confirm the cellular source and magnitude of change by single-nucleus RNA-seq, reverse transcriptase-polymerase chain reaction (RT-PCR), and immunohistochemistry in 61 healthy controls, 63 schizophrenia cases, and 33 bipolar disorder cases stratified into low- and high-inflammation groups. Results: By RNA-seq, the TNF superfamily (TNFSF) pathway messenger RNAs (mRNAs) were among the most changed in high-inflammation schizophrenia (all Conclusions: Our results suggest that TNFSF transcripts represent the main activated inflammatory pathway in the midbrains of people with schizophrenia, which overlaps somewhat with bipolar disorder. These findings highlight the need for anti-inflammatory interventions targeting TNF/TNFSF receptors to test for therapeutic benefits in psychiatric patients displaying elevated inflammation.

Indexed as

Bipolar disorderMidbrainmRNARNA-seqSchizophreniaTNFSF

Identifiers

PMID41567988
PMCPMC12818133

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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.