Evidence map›Paper›PMID 39803900›Full record

ArticleThe international journal of neuropsychopharmacology2025

Investigation of the mesencephalic astrocyte-derived neurotrophic factor-endoplasmic reticulum stress pathway in mood disorders.

Mohammad Ali, Bianca Wollenhaupt-Aguiar, Yifan Wang, Fahed Abu-Hijleh, Nicolette Rigg, Taiane de Azevedo Cardoso, Imran Ahmed, Ridhi Gopalakrishnan, Karen Jansen, Luciano Dias de Mattos Souza and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The international journal of neuropsychopharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

19 authors.

Mohammad AliMiNDS Neuroscience Graduate Program, McMaster University, Hamilton, Ontario, Canada.ORCID 0000-0001-7302-460X
Bianca Wollenhaupt-AguiarCentre for Clinical Neurosciences, McMaster University, Hamilton, Ontario, Canada.
Yifan WangCentre for Clinical Neurosciences, McMaster University, Hamilton, Ontario, Canada.
Fahed Abu-HijlehMiNDS Neuroscience Graduate Program, McMaster University, Hamilton, Ontario, Canada.
Nicolette RiggMiNDS Neuroscience Graduate Program, McMaster University, Hamilton, Ontario, Canada.
Taiane de Azevedo CardosoIMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Victoria, Australia.
Imran AhmedDepartment of Biochemistry & Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Ridhi GopalakrishnanCentre for Clinical Neurosciences, McMaster University, Hamilton, Ontario, Canada.
Karen JansenDepartment of Health and Behavior, Catholic University of Pelotas, Pelotas, Brazil.
Luciano Dias de Mattos SouzaDepartment of Health and Behavior, Catholic University of Pelotas, Pelotas, Brazil.
Ricardo Azevedo da SilvaDepartment of Health and Behavior, Catholic University of Pelotas, Pelotas, Brazil.
Thaise Campos MondinDepartment of Student Affairs, Federal University of Pelotas, Pelotas, Brazil.
Flavio KapczinskiDepartment of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada.
Fernanda Pedrotti MoreiraDepartment of Health and Behavior, Catholic University of Pelotas, Pelotas, Brazil.
Andrew LoftsSchool of Biomedical Engineering, McMaster University, West Hamilton, Ontario L8S 4L8, Canada.
William D GwynneDepartment of Surgery, McMaster University, West Hamilton, Ontario L8S 4L8, Canada.
Todd HoareSchool of Biomedical Engineering, McMaster University, West Hamilton, Ontario L8S 4L8, Canada.
Ram MishraDepartment of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada.
Benicio N FreyCentre for Clinical Neurosciences, McMaster University, Hamilton, Ontario, Canada.ORCID 0000-0001-8267-943X

Funding

Milken Institute-Baszucki Brain Research Fund Bipolar Disorder Grant BD-0000000133
6 · The paper itself

Abstract

backgroundBipolar disorder (BD) has been associated with impaired cellular resilience. Recent studies have shown abnormalities in the unfolded protein response (UPR) in BD. The UPR is the cellular response to endoplasmic reticulum (ER) stress. Mesencephalic astrocyte-derived neurotrophic factor (MANF), a trophic factor, decreases ER stress by modulating the UPR. The objective of this study is to investigate the MANF-ER stress pathway in BD and major depressive disorder (MDD) compared to healthy controls (HC).

methodsMANF protein concentration and MANF and GRP78 gene expression were assessed in peripheral blood from individuals with BD, MDD, and HC (protein: 40 BD, 55 MDD, 55 HC; gene expression: 52 BD, 61 MDD, 69 HC). MANF protein and gene expression along with GRP78 gene expression were also analyzed in postmortem brain tissue (20 BD, 20 MDD, 19 HC). MANF protein was quantified using an ELISA assay while quantitative polymerase chain reaction was used for MANF and GRP78 gene expression.

resultsPeripheral MANF protein levels were reduced in individuals with BD in a depressive state compared to controls (P = .031) and euthymic BD participants (P = .013). No significant differences in MANF or GRP78 gene expression were observed in BD irrespective of mood state, or MDD compared to HC (all P > .05). No differences were observed regarding MANF/GRP78 protein or gene expression levels in postmortem tissue (P > .05).

conclusionsIndividuals with BD who were in an acute depressive phase were found to have reduced peripheral MANF levels potentially signifying abnormal UPR and supporting the notion that BD is associated with increased ER stress.

Indexed as

Bipolar DisorderEndoplasmic Reticulum StressMajor Depressive DisorderNerve Growth FactorsReceptors, G-Protein-CoupledAdultAutopsyBrainFemaleHumansMaleMiddle AgedYoung AdultGPR78 protein, humanMANF protein, humanNerve Growth FactorsReceptors, G-Protein-Coupledbipolar disorderendoplasmic reticulum (ER) stressGRP78MANFMDDmood disordersUPR

Identifiers

PMID39803900
PMCPMC11808195

What Socratic holds

Textmetadata
LicenceCC BY-NC
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 Socratic graph.