Evidence map›Paper›PMID 26133963›Full record

ArticleThe American journal of psychiatry2015

Molecular mechanisms and timing of cortical immune activation in schizophrenia.

David W Volk, Anjani Chitrapu, Jessica R Edelson, Kaitlyn M Roman, Annie E Moroco, David A Lewis

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The American journal of psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed, 6 pooled it
4.3field-weighted citation impact, top 4% of its field
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

74 citing papers in PubMed, 6 syntheses or guidelines pooled it, 125 citations in OpenAlex.

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  7. Psychiatric Genomics 2025: State of the Art and the Path Forward.The Psychiatric clinics of North America · 2025
    Review
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14 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

David W VolkFrom the Departments of Psychiatry and Neuroscience, University of Pittsburgh, Pittsburgh, Pa.
Anjani ChitrapuFrom the Departments of Psychiatry and Neuroscience, University of Pittsburgh, Pittsburgh, Pa.
Jessica R EdelsonFrom the Departments of Psychiatry and Neuroscience, University of Pittsburgh, Pittsburgh, Pa.
Kaitlyn M RomanFrom the Departments of Psychiatry and Neuroscience, University of Pittsburgh, Pittsburgh, Pa.
Annie E MorocoFrom the Departments of Psychiatry and Neuroscience, University of Pittsburgh, Pittsburgh, Pa.
David A LewisFrom the Departments of Psychiatry and Neuroscience, University of Pittsburgh, Pittsburgh, Pa.
University of Pittsburgh · US

Funding

Schizophrenia and synaptic pruning: Circuit specificity and functional consequencesR01MH051234 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEWIS, DAVID A · 1995 to 2020
$8.5M
SCHIZOPHRENIA AND CORTICAL DOPAMINE/GABA INTERACTIONSR01MH043784 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEWIS, DAVID A · 1988 to 2023
$7.2M
GABA Neurons and Cortical Circuitry in SchizophreniaR37MH043784 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEWIS, DAVID A · 2001 to 2010
$6.8M
Disrupted Ontogeny of Cortical GABA Neurons in SchizophreniaR01MH100066 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI VOLK, DAVID W · 2014 to 2018
$2.2M
NIMH NIH HHS MH043784NIMH NIH HHS MH051234NIMH NIH HHS MH100066NIMH NIH HHS R01 MH043784NIMH NIH HHS R01 MH051234NIMH NIH HHS R01 MH100066NIMH NIH HHS R37 MH043784
6 · The paper itself

Abstract

objectiveImmune-related abnormalities are commonly reported in schizophrenia, including higher mRNA levels for the viral restriction factor interferon-induced transmembrane protein (IFITM) in the prefrontal cortex. The authors sought to clarify whether higher IFITM mRNA levels and other immune-related disturbances in the prefrontal cortex are the consequence of an ongoing molecular cascade contributing to immune activation or the reflection of a long-lasting maladaptive response to an in utero immune-related insult.

methodQuantitative polymerase chain reaction was employed to measure mRNA levels for immune-related cytokines and transcriptional regulators, including those reported to regulate IFITM expression, in the prefrontal cortex from 62 schizophrenia and 62 healthy subjects and from adult mice exposed prenatally to maternal immune activation or in adulthood to the immune stimulant poly(I:C).

resultsSchizophrenia subjects had markedly higher mRNA levels for interleukin 6 (IL-6) (+379%) and interferon-β (+29%), which induce IFITM expression; lower mRNA levels for Schnurri-2 (-10%), a transcriptional inhibitor that lowers IFITM expression; and higher mRNA levels for nuclear factor-κB (+86%), a critical transcription factor that mediates cytokine regulation of immune-related gene expression. In adult mice that received daily poly(I:C) injections, but not in offspring with prenatal exposure to maternal immune activation, frontal cortex mRNA levels were also markedly elevated for IFITM (+304%), multiple cytokines including IL-6 (+493%), and nuclear factor-κB (+151%).

conclusionsThese data suggest that higher prefrontal cortex IFITM mRNA levels in schizophrenia may be attributable to adult, but not prenatal, activation of multiple immune markers and encourage further investigation into the potential role of these and other immune markers as therapeutic targets in schizophrenia.

Indexed as

AdultAnimalsAntigens, DifferentiationCase-Control StudiesCerebral CortexDisease Models, AnimalDNA-Binding ProteinsFemaleGene Expression RegulationHumansInterferon-betaInterferon InducersInterleukin-6MaleMembrane ProteinsMiceAntigens, DifferentiationDNA-Binding Proteinsfragilis3 protein, mousefragilis protein, mouseHIVEP2 protein, humanIFITM2 protein, humanIFITM3 protein, humanInterferon-betaInterferon InducersInterleukin-6leu-13 antigenMembrane ProteinsNF-kappa BPoly I-CRNA-Binding ProteinsRNA, MessengerTranscription Factors

Identifiers

PMID26133963
PMCPMC5063256
OpenAlexW2141078817

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.