Evidence map›Paper›PMID 40265626›Full record

ArticleBipolar disorders2025

Plasma Glial Fibrillary Acidic Protein and Neurofilament Light Are Elevated in Bipolar Depression: Evidence for Neuroprogression and Astrogliosis.

Matthew J Y Kang, Dhamidhu Eratne, Olivia Dean, Michael Berk, Adam J Walker, Cassandra Wannan, Charles B Malpas, Claudia Cicognola, Shorena Janelidze, Oskar Hansson and 6 more

Abstract read
In one paragraph

Article in Bipolar disorders, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Article
  2. Plasma GFAP modifies the association of depressive symptoms with cognitive function: A population-based study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Preliminary Investigation of the Association Between Epigenetic Aging Acceleration and Amyloid Biomarkers in Bipolar Disorder.The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry · 2026
    Article
  9. Article
  10. 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

16 authors.

Matthew J Y KangNeuropsychiatry Centre, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.ORCID 0000-0001-9375-3762
Dhamidhu EratneNeuropsychiatry Centre, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.ORCID 0000-0002-3226-7645
Olivia DeanInstitute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine, Deakin University and Barwon Health, Geelong, Victoria, Australia.ORCID 0000-0002-2776-3935
Michael BerkInstitute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine, Deakin University and Barwon Health, Geelong, Victoria, Australia.ORCID 0000-0002-5554-6946
Adam J WalkerInstitute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine, Deakin University and Barwon Health, Geelong, Victoria, Australia.ORCID 0000-0002-5399-1245
Cassandra WannanOrygen, Parkville, Victoria, Australia.ORCID 0000-0003-1317-4635
Charles B MalpasMelbourne School of Psychological Sciences, The University of Melbourne, Melbourne, Victoria, Australia.
Claudia CicognolaClinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden.
Shorena JanelidzeClinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden.
Oskar HanssonClinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden.
Jasleen GrewalAlfred Mental and Addiction Health, Alfred Health, Melbourne, Victoria, Australia.
Philip B MitchellDiscipline of Psychiatry and Mental Health, School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia.ORCID 0000-0002-7954-5235
Malcolm HopwoodDepartment of Psychiatry, The University of Melbourne, Parkville, Victoria, Australia.ORCID 0000-0001-6004-4521
Christos PantelisDepartment of Psychiatry, The University of Melbourne, Parkville, Victoria, Australia.ORCID 0000-0002-9565-0238
Alexander F SantilloClinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden.ORCID 0000-0001-9717-0820
Dennis VelakoulisNeuropsychiatry Centre, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.ORCID 0000-0002-8842-8479

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRecent advances now allow detection of brain-specific proteins in blood, including neurofilament light chain (NfL), a marker of axonal pathology, and glial fibrillary acidic protein (GFAP), indicative of astrocytic activation. Given the evidence of astroglial pathology and neuronal dysfunction in bipolar disorder, and ongoing debates on neuroprogression, we investigated plasma NfL and GFAP levels in affected individuals.

methodsThis study analysed plasma NfL and GFAP measured in 216 individuals using Simoa. We used bootstrapped general linear models (GLM) to compare plasma NfL and GFAP levels between people with bipolar depression (n = 120) and healthy controls (n = 96), adjusting for age, sex, and weight. We examined associations between these biomarkers and clinical variables while adjusting for multiple comparisons. For sensitivity analyses, predictors were evaluated using Bayesian model averaging (BMA).

resultsPlasma GFAP (β = 0.21 [0.07, 0.35], p = 0.006) and NfL (β = 0.06 [0.01, 0.10], p = 0.028) were elevated in people with bipolar depression. Illness duration was positively associated with NfL (r = 2.97, p = 0.002), and further supported by BMA analysis (posterior inclusion probability, PIP = 0.85). Age of onset was positively associated with GFAP (r = 0.246 p = 0.041), which was also supported by BMA analysis (PIP = 0.67).

conclusionsThese findings indicate increased plasma NfL and GFAP levels in bipolar disorder. Our findings support the neuroprogression hypothesis, where prolonged illness duration contributes to neuroaxonal damage. Elevated GFAP in those with later onset suggests a role for neuroinflammation, potentially linked to increased cardiovascular and metabolic comorbidities.

Indexed as

Bipolar DisorderGlial Fibrillary Acidic ProteinGliosisNeurofilament ProteinsAdultBiomarkersDisease ProgressionFemaleHumansMaleMiddle AgedBiomarkersGFAP protein, humanGlial Fibrillary Acidic Proteinneurofilament protein LNeurofilament Proteinsbiological markersbipolar disorderdepressionglial fibrillary acidic proteinmaniamental healthneurofilament light chainpsychiatry

Identifiers

PMID40265626
PMCPMC12397446

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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.