Evidence map›Paper›PMID 33491066›Full record

SynthesisSchizophrenia bulletin2021

Matrix Metalloproteinase 9 Blood Alterations in Patients With Schizophrenia Spectrum Disorders: A Systematic Review and Meta-Analysis.

Georgios Schoretsanitis, Renato de Filippis, Maria Ntogka, Stefan Leucht, Christoph U Correll, John M Kane

Open access · bronzeAbstract readMeta-AnalysisSystematic Review
In one paragraph

Synthesis in Schizophrenia bulletin, 2021. 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
2.3field-weighted citation impact, top 12% 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

10 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. ALife science alliance · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Observational
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

6 authors at 5 institutions in 5 countries.

Georgios SchoretsanitisDepartment of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA.ORCID 0000-0002-3851-4117
Renato de FilippisPsychiatric Unit, Department of Health Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy.ORCID 0000-0001-6928-1224
Maria NtogkaDepartment of Biology, University of Crete, Heraklion, Crete, Greece.
Stefan LeuchtDepartment of Psychiatry and Psychotherapy, School of Medicine, Technical University of Munich, Munich, Germany.
Christoph U CorrellDepartment of Psychiatry and Molecular Medicine, The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA.
John M KaneDepartment of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA.
Northwell Health · USFeinstein Institute for Medical Research · USKing's College London · GBMagna Graecia University · ITUniversity of Crete · GR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMatrix metalloproteinase 9 (MMP-9), an extracellular network protease implicated in glutamatergic signaling, may be part of the pathophysiology of schizophrenia spectrum disorders (SSD).

methodsWe performed a systematic review in PubMed/Embase until July 15, 2020, conducting a random-effects meta-analysis of studies comparing MMP-9 blood levels in SSD vs healthy controls (HCs) and psychiatric controls (PCs), calculating between-group differences in standardized mean differences (SMDs) ± 95% confidence intervals (CIs). Meta-regression analyses included sex, age, illness duration, antipsychotic dose, and Positive and Negative Syndrome Scale (PANSS) total/subscales. Subgroup analyses included first-episode patients (FEP) vs non-FEP, each vs HCs and vs PCs, and blood sample type. Study quality was assessed using the Newcastle-Ottawa scale.

resultsFour, five, and two trials were rated as high, fair, and low quality. In 11 studies (n = 1443), 643 patients (age = 36.7 ± 14.1 years, females = 42.9%) were compared with HCs (n = 631), with 4 studies including also 169 PCs. MMP-9 levels were higher in SSD vs HCs (SMD = 0.52, 95%CI = 0.20-0.85, P = .002), but not in PCs vs HCs (n = 132, after removing one implausible outlier [SMD = 0.33, 95%CI = -0.16 to 0.85, P = .082]). MMP-9 differences between SSD and HCs were associated with higher PANSS total (coefficient = 0.02, 95%CI = 0.01-0.02, P < .001), PANSS positive (coefficient = 0.08, 95%CI = 0.02-0.13, P = .006), and PANSS general scores (coefficient = 0.02, 95%CI = 0.01-0.03, P < .001). MMP-9 level differences vs HCs did not vary significantly between FEP (n = 103, SMD = 0.44, 95%CI = 0.15-0.72, P = .71) and non-FEP patients (n = 466, SMD = 0.59, 95%CI = 0.38-0.80; P = .34) (FEP vs non-FEP: P = .39). In four high-quality studies, MMP-9 levels remained significantly higher in SSD vs HCs (SMD = 0.82, 95%CI = 0.03-1.61).

conclusionsFindings suggest MMP-9 upregulation in SSD, requiring further validation and understanding of related pathways.

Indexed as

HumansMatrix Metalloproteinase 9SchizophreniaMatrix Metalloproteinase 9glutamatergic transmissionmatrix metalloproteinase 9 (MMP-9)neuroimmunologyoxidative stressschizophrenia spectrum disorders (SSD)

Identifiers

PMID33491066
PMCPMC8266643
OpenAlexW3126122972

What OpenQuestion holds

Textmetadata
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.