Evidence map›Paper›PMID 42901887›Full record

ArticleTranslational psychiatry2026

Association between clozapine-induced hypertriglyceridemia and defenestration of liver sinusoidal endothelial cells.

Tetyana Voloshyna, Øyvind V Svendsen, Karolina Szafranska, Jakub Pospíšil, Eike C Struck, Elisabet Størset, Robert L Smith, Espen Molden, David G Le Couteur, Victoria C Cogger and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Translational psychiatry, 2026. 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

12 authors.

Tetyana Voloshyna *Vascular Biology Research Group, Department of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway.
Øyvind V Svendsen *Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway.ORCID http://orcid.org/0000-0001-5665-6904
Karolina SzafranskaVascular Biology Research Group, Department of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway.
Jakub PospíšilVascular Biology Research Group, Department of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway.
Eike C StruckTranslational Vascular Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
Elisabet StørsetCenter for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.
Robert L SmithCenter for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.
Espen MoldenCenter for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.ORCID http://orcid.org/0000-0001-6190-2751
David G Le CouteurANZAC Research Institute, Concord Hospital, Sydney Local Health District and Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
Victoria C CoggerANZAC Research Institute, Concord Hospital, Sydney Local Health District and Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
Peter A G McCourtVascular Biology Research Group, Department of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway.ORCID http://orcid.org/0000-0001-5072-4590
Erik S DietrichsInstitute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway. eriksdi@uio.no.ORCID http://orcid.org/0000-0002-5679-9937

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Clozapine is the most effective antipsychotic drug, while also causing the most severe metabolic side effects. The underlying mechanisms of these side effects appear multifactorial and are not entirely understood. We hypothesized that liver sinusoidal endothelial cells (LSEC) dysfunction is linked to the metabolic side effects of clozapine, based on known association between reduced LSEC porosity, hypertriglyceridemia and insulin resistance. Accordingly, we conducted a translational study by assessing the porosity of murine LSECs following clozapine exposure in vitro and correlating serum clozapine concentrations with metabolic parameters in routine human blood samples. The patient data showed a correlation for clozapine serum concentrations with both triglycerides (Spearman's ρ = 0.47, P = 0.00024) and glucose levels (ρ = 0.24, P = 0.034), but no correlation with LDL cholesterol (ρ = -0.04, P = 0.82) or HDL cholesterol (ρ = -0.22, P = 0.088). The in vitro experiments showed a concentration-dependent reduction in murine LSEC porosity (P for trend = 0.00036). Together, these findings support a link between clozapine exposure and reduced LSEC porosity. This represents a promising point of intervention that potentially could expand safe access to clozapine as a highly effective antipsychotic treatment for a broader population, also in individuals at high risk for metabolic and cardiovascular side effects.

Indexed as

Antipsychotic AgentsClozapineEndothelial CellsHypertriglyceridemiaLiverAdultAnimalsFemaleHumansMaleMiceMice, Inbred C57BLMiddle AgedTriglyceridesAntipsychotic AgentsClozapineTriglycerides

Identifiers

PMID42901887
PMCPMC13683405

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.