The Antipsychotic Risperidone Alters Dihydroceramide and Ceramide Composition and Plasma Membrane Function in Leukocytes In Vitro and In Vivo
Open accessAbstract
Atypical or second-generation antipsychotics are used in the treatment of psychosis and behavioral problems in older persons with dementia. However, these pharmaceutical drugs are associated with an increased risk of stroke in such patients. In this study, we evaluated the effects of risperidone treatment on phospholipid and sphingolipid composition and lipid raft function in peripheral blood mononuclear cells (PBMCs) of older patients (mean age >88 years). The results showed that the levels of dihydroceramides, very-long-chain ceramides, and lysophosphatidylcholines decreased in PBMCs of the risperidone-treated group compared with untreated controls. These findings were confirmed by in vitro assays using human THP-1 monocytes. The reduction in the levels of very-long-chain ceramides and dihydroceramides could be due to the decrease in the expression of fatty acid elongase 3, as observed in THP-1 monocytes. Moreover, risperidone disrupted lipid raft domains in the plasma membrane of PBMCs. These results indicated that risperidone alters phospholipid and sphingolipid composition and lipid raft domains in PBMCs of older patients, potentially affecting multiple signaling pathways associated with these membrane domains.
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Antipsychotics increase LDL receptor transcription, thereby stimulating LDL endocytosis and exacerbating the intracellular accumulation of LDL-derived lipids.
“In addition, antipsychotics increase LDL receptor transcription, thereby stimulating LDL endocytosis and exacerbating the intracellular accumulation of LDL-derived lipids [136].”
From Lipids in Psychiatric Disorders: Functional and Potential Diagnostic Role as Blood Biomarkers (2024) · cites this paper as [136]
Antipsychotics disrupt intracellular cholesterol trafficking by inhibiting cholesterol efflux from endolysosomes, thereby reducing the transport of endocytosed LDL cholesterol into the endoplasmic reticulum and Golgi apparatus.
“In addition, antipsychotics disrupt intracellular cholesterol trafficking by inhibiting cholesterol efflux from endolysosomes, thereby reducing the transport of endocytosed LDL cholesterol into the endoplasmic reticulum and Golgi apparatus [136].”
From Lipids in Psychiatric Disorders: Functional and Potential Diagnostic Role as Blood Biomarkers (2024) · cites this paper as [136]
SCZ patients treated with risperidone show decreased levels of dihydroceramide, very long-chain Cers, and lysoPC in mononuclear cells.
“SCZ patients treated with risperidone showed decreased levels of dihydroceramide, very long-chain Cers, and lysoPC in mononuclear cells [136].”
From Lipids in Psychiatric Disorders: Functional and Potential Diagnostic Role as Blood Biomarkers (2024) · cites this paper as [136]
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References 46 · Cited by 11
- Authors
- Canfrán-Duque, A., Pastor, Ó., García-Seisdedos, D., Molina, Y. L., Babiy, B., Lerma, M., Sánchez-Castellano, C., Martínez-Botas, J., Gómez-Coronado, D., Lasunción, M. A., Cruz-Jentoft, A. J., & Busto, R.
- Affiliations
- Servicio de Bioquímica-Investigación, Hospital Universitario Ramón y Cajal, IRyCIS, 28034 Madrid, Spain
- Instituto de Salud Carlos III (ES)
- Instituto Ramón y Cajal de Investigación Sanitaria (ES)
- Corresponding author
- Cruz-Jentoft, Alfonso J.
- Busto, Rebeca
- ORCID
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2021-04-10
- Volume
- 22
- Issue
- 8
- Pages
- 3919
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC8069118
- OpenAlex
- W3156900549
- Cited by
- 11
- References
- 46
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 5 · 2022: 1 · 2021: 1
- FWCI
- 0.78
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Ministerio de Ciencia e Innovación (SAF2015-70747-R, RTI2018-098113-B-I00)
- Instituto de Salud Carlos III (PI18/01152)
- Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición (MA Lasuncion)
- Consejería de Educación e Investigación (PEJD-2017-PRE/BMD-4142, PEJD-2019-PRE/BMD-15962, PEJD-2019-PRE/SAL-16152)
- Consejería de Sanidad, Comunidad de Madrid (Emeritus to MA Lasuncion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- risperidone, atypical antipsychotics, dihydroceramide, ceramide, sphingolipids, phospholipids, lipid rafts, peripheral blood mononuclear cells, THP-1 cells, very long-chain ceramides, lysophosphatidylcholine, plasma membrane, older adults, dementia, stroke risk
- MeSH terms
- Olanzapine, Aged, Aged, 80 and over, Cell Membrane, Ceramides, Female, Humans, Leukocytes, Mononuclear, Lysophospholipids, Male, Psychotic Disorders, Sphingolipids, Antipsychotic Agents, Risperidone, Lipid Metabolism
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